A Validation of the Korean Version of Ultra-Short Suicidal Ideation Scale / 신경정신의학

Objectives@#An accurate and easy-to-identify form is needed for the early evaluation of suicidal ideation in high-risk patients. Therefore, this study examined the validity and reliability of a Korean version of the Ultra-Short Suicidal Ideation Scale (K-USSIS). @*Methods@#A total of 161 psychiatric university-affiliated general hospital patients completed the K-USSIS. The data were analyzed using correlation, internal consistency, and confirmatory factor analyses. @*Results@#First, the scale had good internal consistency with a Cronbach’s α of 0.94. Second, the confirmatory factor analysis demonstrated that the single-factor model had a reasonable fit (comparative fit index=0.99, Tucker–Lewis index=0.98, standardized root mean squared residual=0.01, and root mean square error of approximation=0.10). Finally, the convergent validity analysis revealed a significant positive correlation with depression, anxiety, and hopelessness. @*Conclusion@#The findings suggest that the K-USSIS has good psychometric properties and can serve as a valuable tool for screening for suicidal ideation to ensure early intervention in Korean psychiatric patients.

Current Pharmacogenetics in Psychiatry

Pharmacogenetics is opening a new era of precision medicine in psychiatry. Drug-metabolizing enzymes are characterized by genetic polymorphisms, which render a large portion of variability in individual drug metabolism. Dose adjustment based on pharmacogenetics knowledge is a first step to translate pharmacogenetics into clinical practice. However, diverse factors including cost-effectiveness should be addressed to provide clinical recommendation. To address current challenges in pharmacogenetics testing in psychiatry, this review provides an update regarding genotyping (SNP analysis, array, and next-generation sequencing), genotype-phenotype correlations, and cost-effectiveness. The current updates on pharmacogenetics in psychiatry will provide guidance for both clinician and researchers to have a consensus in harmonizing efforts to advance the pharmacogenetics field in a part of precision medicine in psychiatry.

Current Pharmacogenetics in Psychiatry

Pharmacogenetics is opening a new era of precision medicine in psychiatry. Drug-metabolizing enzymes are characterized by genetic polymorphisms, which render a large portion of variability in individual drug metabolism. Dose adjustment based on pharmacogenetics knowledge is a first step to translate pharmacogenetics into clinical practice. However, diverse factors including cost-effectiveness should be addressed to provide clinical recommendation. To address current challenges in pharmacogenetics testing in psychiatry, this review provides an update regarding genotyping (SNP analysis, array, and next-generation sequencing), genotype-phenotype correlations, and cost-effectiveness. The current updates on pharmacogenetics in psychiatry will provide guidance for both clinician and researchers to have a consensus in harmonizing efforts to advance the pharmacogenetics field in a part of precision medicine in psychiatry.

Social Stigmata of Electroconvulsive Therapy and Their Reduction Strategies

Modified electroconvulsive therapy (ECT) which started in 1950s is a safe and efficacious treatment for several mental disorders including mood disorders and psychotic disorders. However, its usage in present days is still limited by misconceptions and stigmata of ECT. This paper overviews the background from which the stigmata of ECT stemmed and the current status of stigmata surrounding ECT among the public and medical professionals. In addition, a few potential strategies for reducing stigmata of ECT are provided in this review.

Social Stigmata of Electroconvulsive Therapy and Their Reduction Strategies

Modified electroconvulsive therapy (ECT) which started in 1950s is a safe and efficacious treatment for several mental disorders including mood disorders and psychotic disorders. However, its usage in present days is still limited by misconceptions and stigmata of ECT. This paper overviews the background from which the stigmata of ECT stemmed and the current status of stigmata surrounding ECT among the public and medical professionals. In addition, a few potential strategies for reducing stigmata of ECT are provided in this review.

Public Attention to Crime of Schizophrenia and Its Correlation with Use of Mental Health Services in Patients with Schizophrenia / 대한정신분열병학회지

OBJECTIVES: This study was performed to examine the effects of the public attention to ‘crime of schizophrenia’ on the use of mental health services in patients with schizophrenia using big data analysis. METHODS: Data on the frequency of internet searches for ‘crime of schizophrenia’ and the patterns of mental health service utilization by patients with schizophrenia spectrum disorders by month were collected from Naver big data and the Health Insurance Review and Assessment Services in Korea, respectively. Their correlations in the same and following month for lagged effect were examined. RESULTS: The number of outpatients correlated negatively with public attention to ‘crime of schizophrenia’ in the same month. The lagged relationship between public attention and the number of admissions in psychiatric wards was also found. In terms of sex differences, the use of outpatient services among female patients correlated negatively with public attention in the same month while the number of male patients' admissions in both same and following month correlated positively with public attention. CONCLUSION: These findings suggested that public attention to ‘crime of schizophrenia’ could negatively affect illness behavior in patients with schizophrenia.

Association between a Genetic Variant of CACNA1C and the Risk of Schizophrenia and Bipolar I Disorder Across Diagnostic Boundaries / 대한정신분열병학회지

OBJECTIVES: Genome-wide association studies (GWASs) and meta-analyses indicate that single-nucleotide polymorphisms (SNPs) in the a-1C subunit of the L-type voltage-dependent calcium channel (CACNA1C) gene increase the risk for schizophrenia and bipolar disorders (BDs). We investigated the association between the genetic variants on CACNA1C and schizophrenia and/or BDs in the Korean population. METHODS: A total of 582 patients with schizophrenia, 336 patients with BDs consisting of 179 bipolar I disorder (BD-I) and 157 bipolar II disorder (BD-II), and 502 healthy controls were recruited. Based on previous results from other populations, three SNPs (rs10848635, rs1006737, and rs4765905) were selected and genotype-wise association was evaluated using logistic regression analysis under additive, dominant and recessive genetic models. RESULTS: rs10848635 showed a significant association with schizophrenia (p=0.010), the combined schizophrenia and BD group (p=0.018), and the combined schizophrenia and BD-I group (p=0.011). The best fit model was dominant model for all of these phenotypes. The association remained significant after correction for multiple testing in schizophrenia and the combined schizophrenia and BD-I group. CONCLUSION: We identified a possible role of CACNA1C in the common susceptibility of schizophrenia and BD-I. However no association trend was observed for BD-II. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

Effects of Renaming Schizophrenia in Korea: from “Split-Mind Disorder” to “Attunement Disorder”

OBJECTIVE: Korean Neuropsychiatric Association changed the Korean name of schizophrenia from ‘Split-mind Disorder’ to ‘Attunement Disorder’ in 2012. This study assessed attitudes towards the renaming of schizophrenia among mental health practitioners (n=440), patients with schizophrenia and their guardians (n=396), and the university students (n=140) using self-administered questionnaires. METHODS: The questionnaire included items related to participants’ perception of the renaming of the disease, the nature of informing about the disease to confirm the effect of the name change. RESULTS: It was confirmed the notification rate of disease name by mental health practitioners was increased significantly after the renaming. Among patients and their guardians, 24.9% and 15.0%, respectively, perceived their own or the family member’s illness as ‘attunement disorder’. CONCLUSION: Patients and their guardians continue to display a low awareness about the name of the disease as ‘attunement disorder.’ However, mental health practitioners were found to be able to easily use the name ‘attunement disorder’ as a result of the increased notification rate of the new disease name.

The Association of the 2nd to 4th Digit Ratio with the Age of Onset and Metabolic Factors in Korean Patients with Schizophrenia

OBJECTIVES: The ratio of second to fourth digit length (2D : 4D) could be a potential epigenetic marker of sexual dimorphism reflecting prenatal testosterone exposure. Testosterone is known to affect the development of the brain through an epigenetic mechanism. The purpose of this study was to investigate the effects of exposure to fetal testosterone on the metabolic syndrome based on 2D : 4D of schizophrenia patients and the relationship with the age of onset of schizophrenia. METHODS: A total of 214 schizophrenia patients participated in this study. The participant's physical and blood tests were performed according to the American National Cholesterol Education Program's Third Amendment of the Metabolic Syndrome Diagnostic Criteria, and the 2D : 4D was measured by the method designed by McFadden. Data were statistically analyzed by t-test, Pearson's correlation analysis and multiple regression model analysis. RESULTS: 2D : 4D was significantly higher in female than male in both hands, and there was a statistically significant negative correlation between 2D : 4D and the age of onset of schizophrenia in male. However, 2D : 4D did not show statistically significant correlation with metabolic factors. CONCLUSIONS: Fetal testosterone suggests the possibility of affecting the age of onset of schizophrenia through the epigenetic mechanism, but there is no clear relationship with metabolic factors.

Prevalence of Metabolic Syndrome in Patients with Schizophrenia in Korea: A Multicenter Nationwide Cross-Sectional Study

OBJECTIVE: We designed a nationwide study with limited exclusion criteria to investigate the prevalence of metabolic syndrome (MetS) in Korea and its relationship with antipsychotic medications. METHODS: This multicenter, cross-sectional, and observational study included patients diagnosed with schizophrenia or schizoaffective disorder. Sixteen hospitals enrolled 845 patients aged 18 to 65 years prescribed any antipsychotic medication between August 2011 and August 2013. MetS was diagnosed using the criteria of the modified Adult Treatment Panel III of the National Cholesterol Education Program with the Korean abdominal obesity definition (waist circumference ≥85 cm in women, ≥90 cm in men). RESULTS: The prevalence of MetS in all patients was 36.5% and was significantly higher in men than women (men, 40.8%; women, 32.2%) and was significantly correlated with age [odds ratio (OR) 1.02] and duration of illness (OR 1.03). The prevalence of MetS across antipsychotic drugs in the major monotherapy group was as follows: 18.8% for quetiapine, 22.0% for aripiprazole, 33.3% for both amisulpride and paliperidone, 34.0% for olanzapine, 35% for risperidone, 39.4% for haloperidol, and 44.7% for clozapine. CONCLUSION: The prevalence of MetS is very high in patients with schizophrenia or schizoaffective disorder. Screening and monitoring of MetS is also strongly recommended.

A Study of Neurological Soft Signs in Patients with Schizophrenia and Their Unaffected Siblings

OBJECTIVES: This study was conducted to investigate the possibility of neurological soft signs as an endophenotype for schizophrenia by examining neurological soft signs in patients, their unaffected siblings and normal comparison subjects. METHODS: The study sample consisted of 32 patients, 25 of their unaffected siblings and 30 normal comparison subjects. Neurological soft signs were evaluated using the Cambridge Neurological Inventory Part 2. soft sign assessment. RESULTS: The patients were significantly more impaired than normal comparison subjects (p = 0.047) on primitive reflex. The patients were significantly more impaired than siblings (p = 0.004) and normal comparison subjects (p = 0.021) on motor coordination. The siblings performed better on sensory integration than the patients (p = 0.020) and normal comparison subjects (p = 0.036). CONCLUSIONS: This study suggests that neurological soft signs might be a potential biomarker for schizophrenia, but might not be an endophenotype for schizophrenia.

The Ratio of 2nd to 4th Digit Length in Korean Alcohol-dependent Patients

OBJECTIVE: The ratio of 2nd to 4th digit length (2D:4D) is a sexually dimorphic trait. Men have a relatively shorter second digit than fourth digit. This ratio is thought to be influenced by higher prenatal testosterone level or greater sensitivity to androgen. The purpose of this study is to investigate the relationship between alcohol dependence and 2D:4D in a Korean sample and whether 2D:4D can be a biologic marker in alcohol dependence. METHODS: In this study, we recruited 87 male patients with alcohol dependence from the alcohol center of one psychiatric hospital and 52 healthy male volunteers who were all employees in the same hospital as controls. We captured images of the right and left hands of patients and controls using a scanner and extracted data with a graphics program. We measured the 2D:4D of each hand and compared the alcohol dependence group with the control group. We analyzed these ratios using an independent-samples t-test. RESULTS: The mean 2D:4D of patients was 0.934 (right hand) and 0.942 (left hand), while the mean 2D:4D of controls was 0.956 (right hand) and 0.958 (left hand). Values for both hands were significantly lower for patients than controls (p<0.001, right hand; p=0.004, left hand). CONCLUSION: Patients who are alcohol dependent have a significantly lower 2D:4D than controls, similar to the results of previous studies, which suggest that a higher prenatal testosterone level in the gonadal period is related to alcoholism. Furthermore, 2D:4D is a possible predictive marker of alcohol dependence.

Linkage and Association Analyses of Schizophrenia with Genetic Variations on Chromosome 22q11 in Koreans

OBJECTIVE: Chromosome 22q11 has been implicated as a susceptibility locus of schizophrenia. It also contains various candidate genes for which evidence of association with schizophrenia has been reported. To determine whether genetic variations in chromosome 22q11 are associated with schizophrenia in Koreans, we performed a linkage analysis and case-control association study. METHODS: Three microsatellite markers within a region of 4.35 Mb on 22q11 were genotyped for 47 multiplex schizophrenia families, and a non-parametric linkage analysis was applied. The association analysis was done with 227 unrelated patients and 292 normal controls. For 39 single nucleotide polymorphisms (SNPs) spanning a 1.4 Mb region (33 kb interval) containing four candidate schizophrenia genes (DGCR, COMT, PRODH and ZDHHC8), allele frequencies were estimated in pooled DNA samples. RESULTS: No significant linkage was found at any of the three microsatellite markers in single and multi-point analyses. Five SNPs showed suggestive evidence of association (p<0.05) and two more SNPs showed a trend for association (p<0.1) in pooled DNA association analysis. Individual genotyping was performed for those seven SNPs and four more intragenic SNPs. In this second analysis, all of the 11 SNPs individually genotyped did not show significant association. CONCLUSION: The present study suggests that genetic variations on chromosome 22q11 may not play a major role in Korean schizophrenia patients. Inadequate sample size, densities of genetic markers and differences between location of genetic markers of linkage and association can contribute to an explanation of the negative results of this study.

Association Study of ANK3 Polymorphism and Risk of Schizophrenia

OBJECTIVES: Previous genome-wide association studies have indicated the association between ankyrin 3 (ANK3) and the vulnerability of schizophrenia. We investigated the association between single nucleotide polymorphisms (SNPs) covering the whole ANK3 locus and schizophrenia in the Korean population. METHODS: The study subjects were 582 patients with schizophrenia and 502 healthy controls. Thirty-eight tag SNPs on ANK3 and five additional SNPs showing significant association with schizophrenia in previous studies were genotyped. RESULTS: Three (rs10994181, rs16914791, rs1938526) of 43 SNPs showed a nominally significant association (p < 0.05) with at least one genotype model. But none of these associations remained significant after adjusting for multiple testing errors with Bonferroni's correction. CONCLUSIONS: We could not identify a significant association between ANK3 and schizophrenia in the Korean population. However, three SNPs showing an association signal with nominal significance need to be investigated in future studies with higher statistical power and more specific phenotype crossing the current diagnostic categories.

The Sex-Related Differences of EEG Coherences between Patients with Bipolar Disorder and Controls

OBJECTIVES: Sex hormones exposure during the prenatal period has an effect on cerebral lateralization. Male brains are thought to be more lateralized than female brains. Bipolar disorder was known to show abnormalities in cerebral laterality whose characteristics could be estimated by electroencephalography (EEG) coherences. We studied sex-related differences of EEG coherences between healthy controls and patients with bipolar disorder to examine the sex effects in the genesis of bipolar disorder. METHODS: Participants were 25 patients with bipolar disorder (11 male, 14 female) and 46 healthy controls (23 male, 23 female). EEG was recorded in the eyes closed resting state. To examine dominant EEG coherence associated with sex differences in both groups within five frequency bands (delta, theta, alpha, beta, and gamma) across several brain regions, statistical analyses were performed using analysis of covariance. RESULTS: Though statistically meaningful results were not found, some remarkable findings were noted. Healthy control females showed more increased interhemispheric coherences than control males in gamma frequency band. There were no differences in the intrahemispheric coherences between the healthy control males and females. In patients with bipolar disorder, female dominant pattern in interhemispheric coherences was attenuated compared with healthy control. CONCLUSIONS: Sex differences of EEG coherences, which could be a marker for cerebral laterality, were attenuated in patients with bipolar disorder compared with healthy controls. These results imply that abnormal sex hormone exposure during early development might play some role in the pathogenesis of bipolar disorder.

The Sex-Related Differences of Relationships between 2D : 4D Ratio and Electroencephalographic Coherence in Patients with Schizophrenia Compared with Controls

OBJECTIVES: Prenatal testosterone is known to influence both cerebral laterality and 2nd to 4th digit ratio (2D : 4D). Epigenetic changes are thought to play some role in it. We studied sex-related differences between 2D : 4D and cerebral laterality in patients with schizophrenia and controls to examine the effects of prenatal testosterone in the development of schizophrenia. METHODS: Forty one men (18 schizophrenic patients and 23 controls) and 40 women (17 schizophrenic patients and 23 controls) were recruited from one psychiatric hospital in Korea. The 2D : 4D and electroencephalographic (EEG) coherence in 19 channels (66 pairs of interhemispheric coherence and 54 pairs of intrahemispheric coherence) were measured. The sex-related statistical analyses between 2D : 4D and EEG coherence in controls and patients with schizophrenia were performed using multiple regression. RESULTS: In male patients, the relationship between 2D : 4D and right intrahemispheric EEG coherence showed mainly positive correlation in delta and theta frequency bands, while it showed negative correlation in male controls. In female patients, the relationship between 2D : 4D and interhemispheric EEG coherence showed stronger positive correlation in alpha and beta frequency bands, while it showed weaker positive correlation in female controls. CONCLUSIONS: Low prenatal testosterone may play certain roles in altered correlation between 2D : 4D and cerebral laterality in schizophrenia and the development of schizophrenia by epigenetic mechanism.

Erratum: A Study of the Relationships between the Ratio of 2nd to 4th Digit Length and Cerebral Laterality

We would like to correct the degree for the 2nd author.

Neurobiology of Aggression

Aggression can be defined as 'behavior intended to harm another' which can be seen both from humans and animals. However, trying to understand aggression in a simplistic view may make it difficult to develop an integrated approach. So, we tried to explain aggression in a multidisciplinary approach, affected by various factors such as neuroanatomical structures, neurotransmitter, genes, and sex hormone. Parallel with animal models, human aggression can be understood with two phenomena, offensive aggression and defensive aggression. Neurobiological model of aggression give a chance to explain aggression with an imbalance between prefrontal regulatory influences and hyper-reactivity of the subcortical areas involved in affective evaluation, finally in an aspect of brain organization. Serotonin and GABA usually inhibit aggression and norepinephrine while glutamate and dopamine precipitate aggressive behavior. As there is no one gene which has been identified as a cause of aggression, functions between gene to gene interaction and gene to environment interaction are being magnified. Contributions of sex hormone to aggression, especially molecular biologic interaction of testosterone and regulation of estrogen receptor have been emphasized during the research on aggression. This multidisciplinary approach on aggression with types, neurochemical bases, and animal models can bring integrated interpretation on aggression.

Attunement Disorder : A Disorder of Brain Connectivity

OBJECTIVES: We reviewed cellular and synaptic dysconnectivity, disturbances in micro- and macro- circuitries, and neurodevelopmentally-derived disruptions of neural connectivity in the pathogenesis of schizophrenia. METHOD: We reviewed the selected articles about disturbances in neural circuits which had been proposed as a pathogenetic mechanism of schizophrenia. RESULTS: The literature review reveals that schizophrenia may be a disease related to disturbance in neurodevelopmental mechanism, shown as 'a misconnection syndrome of neural circuit or neural network'. In descriptive psychopathological view, definition of a disorder of brain connectivity has limitation to explain other aspects of schizophrenia including deterministic strictness in thought process. CONCLUSION: Schizophrenia is considered as a disorder of brain connectivity as well as a neurodevelopmental disorder related with genetic and environmental factors. We could make a suggestion that "JoHyeonByung (attunement disorder)" denotes the disturbances of psychic fine-tuning which correspond to the neural correlates of brain dysconnectivity metaphorically.

Sex-Related Differences of EEG Coherences between Patients with Schizophrenia and Healthy Controls

OBJECTIVES: Alteration of epigenetic effects of testosterone during early development was suggested as an ancillary mechanism for the genesis of schizophrenia. EEG coherence was thought to be a marker for cerebral laterality of which important determinant was testosterone during early development. We studied sex-related differences of EEG coherences between patients with schizophrenia and controls to examine the sex effects in the genesis of schizophrenia. METHODS: EEG was recorded in 35 patients with schizophrenia and 46 healthy controls in the eyes closed resting state. Pair-wise EEG coherences were calculated over delta, theta, alpha, beta and gamma frequency bands. To examine the differences of EEG coherence according to sex in each group, ANCOVA was performed using Statistical Analysis system (SAS, Ver 9.3) and R (Ver 2.15.2). RESULTS: Healthy control males showed more increased right intrahemispheric coherences than healthy control females in delta, theta, alpha and beta frequency bands. In patients with schizophrenia, this male dominant pattern in right intrahemispheric coherences was attenuated especially in alpha and beta bands. Healthy control females showed more increased interhemispheric coherences than healthy control males in delta, theta, beta and gamma frequency bands. In patients with schizophrenia, these female dominant patterns in interhemispheric coherences were attenuated especially in delta, theta, and beta bands, which were commonly observed in frontal to central areas. CONCLUSION: Sex differences in resting EEG coherences were attenuated in schizophrenia patients. These results imply that sex-related aberrant cerebral lateralization might exist in patients with schizophrenia, which are partly due to sex hormones via epigenetic mechanisms.